Objective-To determine the risk factors for noninsulin dependent diabetes in a cohort representative ofmiddle aged British men.Design-Prospective study. Subjects and setting-7735 men aged 40-59, drawn from one group practice in each of 24 towns in Britain. Known and probable cases of diabetes at screening (n= 158) were excluded.Main outcome measures-Non-insulin dependent diabetes (doctor diagnosed) over a mean follow up period of 12 8 years.Results-There were 194 new cases of non-insulin dependent diabetes. Body mass index was the dominant risk factor for diabetes, with an age adjusted relative risk (upper fifth to lower fifth) of 11-6; 95% confidence interval 5*4 to 16-8. Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes, relative to the physically inactive men, after adjustment for age and body mass index (0.4; 0*2 to 0.7), an association which persisted in full multivariate analysis. A nonlinear relation between alcohol intake and diabetes was observed, with the lowest risk among moderate drinkers (16-42 units/week) relative to the baseline group of occasional drinkers (0.6; 0 4 to 1.0). Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration, high density lipoprotein cholesterol concentration (inverse association), heart rate, uric acid concentration, and prevalent coronary heart disease.Conclusion-These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes and coronary heart disease and the potential value of an integrated approach to the prevention of these conditions based on the prevention of obesity and the promotion of physical activity.

The findings suggest that vitamin C has antiinflammatory effects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes.

Background: Aging is associated with significant changes in body composition. Body mass index (BMI; in kg/m 2 ) is not an accurate indicator of overweight and obesity in the elderly. Objective: We examined the relation between other anthropometric indexes of body composition (both muscle mass and body fat) and all-cause mortality in men aged 60 -79 y. Design: The study was a prospective study of 4107 men aged 60 -79 y with no diagnosis of heart failure and who were followed for a mean period of 6 y, during which time there were 713 deaths. Results: Underweight men (BMI 18.5) had exceptionally high mortality rates. After the exclusion of these men, increased adiposity [BMI, waist circumference (WC), and waist-to-hip ratio] showed little relation with mortality after adjustment for lifestyle characteristics. Muscle mass [indicated by midarm muscle circumference (MAMC)] was significantly and inversely associated with mortality. After adjustment for MAMC, obesity markers, particularly high WC (102 cm) and waist-to-hip ratio (top quartile), were associated with increased mortality. A composite measure of MAMC and WC most effectively predicted mortality. Men with low WC (ͨ102 cm) and above-median muscle mass showed the lowest mortality risk. Men with WC 102 cm and above-median muscle mass showed significantly increased mortality [age-adjusted relative risk: 1.36; 95% CI: 1.07, 1.74), and this increased to 1.55 (95% CI: 1.01, 2.39) in those with WC 102 and low MAMC. Conclusion: The findings suggest that the combined use of both WC and MAMC provides simple measures of body composition to assess mortality risk in older men.Am J Clin Nutr 2007;86:1339 -46.

Objective: To examine the role of nonfasting serum insulin level and components of the insulin resistance syndrome in the relationship between physical activity and the incidence of coronary heart disease and type 2 diabetes.Methods: Prospective study of 5159 men aged 40 to 59 years with no history of coronary heart disease, type 2 diabetes, or stroke drawn from general practices in 18 British towns. During an average follow-up period of 16.8 years, there were 616 cases of major coronary heart disease events (fatal and nonfatal) and 196 incident cases of type 2 diabetes.Results: After adjustment for potential confounders (lifestyle characteristics and preexisting disease), physical activity was inversely related to coronary heart disease rates, with the lowest rates in the men undertaking moderate physical activity and with no further benefit thereafter. For type 2 diabetes, risk decreased progressively with increasing levels of physical activity. Physical activity was associated with serum insulin level and with factors associated with insulin, ie, heart rate, hyperuricemia, diastolic blood pressure, and high-density lipoprotein cholesterol level, and with ␥-glutamyltransferase level, a possible marker of hepatic insulin resistance. Adjustment for insulin and associated factors made little difference to the relationship between physical activity and risk of coronary heart disease. By contrast, these factors together with ␥-glutamyltransferase level appear to explain a large proportion of the reduction in risk of type 2 diabetes associated with physical activity. Conclusions:The relationship between physical activity and type 2 diabetes appears to be mediated by serum true insulin level and components of the insulin resistance syndrome. However, these factors do not appear to explain the inverse relationship between physical activity and coronary heart disease.

Earlier studies have not resolved the question of whether elevated circulating insulin levels are independently related to the development of coronary heart disease. Previous studies have not used a specific insulin assay and in all but a minority of studies that have addressed this issue it has not been possible to adjust for possible confounding due to high density lipoprotein (HDL) cholesterol. The authors examined the relation between serum insulin concentration and major coronary disease events (fatal and non-fatal myocardial infarction) in the British Regional Heart Study. The data are based on 5,550 men (aged 40-59 years) in 18 towns whose baseline, non-fasting serum samples were analyzed for insulin using a specific enzyme-linked immunoadsorbent assay (ELISA) method. Known diabetics were excluded. At 11.5 years of follow-up, 521 major coronary disease events had occurred, 261 fatal and 260 non-fatal. A nonlinear relation between serum insulin and coronary disease events was observed with an almost twofold increased relative risk in the 10th decile of the serum insulin distribution (> or = 33.8 mU/liter) relative to the 1st to the 9th deciles combined (age-adjusted relative risk (RR) = 1.9, 95% confidence interval (CI) 1.6-2.4). There was some attenuation of this association on cumulative adjustment for a wide range of biologic and life-style coronary disease risk factors, including HDL cholesterol, though it remained significant in the fully adjusted proportional hazards model (RR = 1.6, 95% CI 1.1-2.3). Similar associations between insulin and coronary disease events were seen in men with and without evidence of coronary disease at screening and in men with baseline serum glucose below the 80th percentile. These data are consistent with the hypothesis that a high level of serum insulin (hyperinsulinemia) is atherogenic, with a threshold effect. However, the markedly nonlinear form of the association and the attenuation in multivariate analysis strongly suggest that elevated insulin levels may only be a marker for common etiologic factors in the development of both coronary disease and non-insulin-dependent diabetes mellitus.

BMI and WC are the simple measures of adiposity most strongly associated with metabolic abnormalities in elderly men. Our findings suggest that WC can be used as a complementary measurement to identify health risks in normal-weight and overweight elderly persons.

Context:Prior studies suggested a role for the arginine vasopressin (AVP) system in the pathogenesis of diabetes. Prospective studies on the association between copeptin (the C-terminal fragment of AVP hormone) and incident diabetes are limited.Objective:We have examined the association between plasma copeptin and the risk of incident diabetes in older men.Design:The British Regional Heart Study was a prospective study with an average of 13 years follow-up.Setting:General practices in the United Kingdom were studied.Participants:Participants were 3226 men aged 60 to 79 years with no prevalent diabetes.Outcome:We measured 253 patients with incident diabetes.Results:Copeptin was positively and significantly associated with renal dysfunction, insulin resistance (homeostasis model assessment of insulin resistance), metabolic risk factors (waist circumference, blood pressure, triglycerides, and liver function), C-reactive protein, tissue plasminogen activator, and von Willebrand factor (endothelial dysfunction) but not with plasma glucose. The risk of incident diabetes was significantly elevated only in men in the top fifth of the copeptin distribution (>6.79 pmol/L), and this risk persisted after adjustment for several diabetes risk factors including metabolic risk factors and C-reactive protein (adjusted hazard ratio in the top fifth vs the rest = 1.78 [95% confidence interval, 1.34–2.37]). Risk was markedly attenuated although it remained significant after further adjustment for homeostasis model assessment of insulin resistance and plasma glucose (adjusted hazard ratio = 1.47 [1.11–1.97]). The increased risk was seen even when the analysis was restricted to men with no chronic kidney disease or to men with no impaired fasting glucose (<6.1 mmol/L).Conclusion:Copeptin is associated with a significantly increased risk of diabetes in older men. The association is partly mediated through lower insulin sensitivity. The findings suggest a potential role of the AVP system in diabetes.

An inverse relation between adult height and risk of coronary heart disease (CHD) has been reported in many studies, but the association between adult height and stroke remains uncertain. The authors examined the relation between adult height and risk of stroke and CHD in a prospective study of 7,735 men drawn from general medical practices in 24 towns in England, Wales, and Scotland. The men were followed up for an average of 16.8 years (range, 15.5-18.0 years) between 1978 and 1995. During this period, there were 351 major stroke events (63 fatal, 288 nonfatal) and 1,093 major CHD events (465 fatal, 628 nonfatal). The mean height of the men was 173.3 cm. Total stroke risk was increased only in the men who fell into the lowest quintile of the height distribution (<167.7 cm), with little difference being seen between the other groups. When data were examined separately for fatal and nonfatal events, no relation was seen with nonfatal stroke. An apparent inverse association was seen with fatal stroke, even after adjustment for a wide range of confounding variables, but the number of deaths was small and the trend was not statistically significant (p = 0.17). By contrast, a significant inverse relation was seen between height and risk of major CHD events: Risk decreased progressively with increasing height, even after full adjustment (highest quintile vs. lowest: relative risk (RR) = 0.74, 95% confidence interval (CI) 0.59-0.91; test for trend: p < 0.001). A stronger inverse association was seen with nonfatal CHD events (RR = 0.64, 95% CI 0.49-0.84) than with fatal CHD events (RR = 0.82, 95% CI 0.60-1.11). This study confirms the finding of an inverse association between height and CHD. The inverse association seen for fatal stroke but not nonfatal stroke suggests that height may be related to specific subtypes of stroke. There are different patterns of association between height and stroke and height and CHD. If the apparent association between short stature and increased risk of fatal stroke is confirmed in other prospective studies, this would suggest that different mechanisms underlie the effects of height on stroke and CHD.